1-Methylpiperazine → HCID 86631938, compound

HRID 906061Notes

Reaction equation

HRID 906061 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([C@@H:8]([NH:10][C:11](=[O:17])[O:12][C:13]([CH3:16])([CH3:15])[CH3:14])[CH3:9])=[CH:4][CH:3]=1.[CH3:18][N:19]1[CH2:24][CH2:23][NH:22][CH2:21][CH2:20]1.C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>COCCOC.C(OCC)(=O)C.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH3:18][N:19]1[CH2:24][CH2:23][N:22]([C:2]2[CH:7]=[CH:6][C:5]([C@@H:8]([NH:10][C:11](=[O:17])[O:12][C:13]([CH3:16])([CH3:15])[CH3:14])[CH3:9])=[CH:4][CH:3]=2)[CH2:21][CH2:20]1

Participants

8

Reactant 4

HCID 531671-MethylpiperazineHCID 62657Potassium Phosphate, TribasicHCID 634876Binap, (A+-)-HCID 56973617(S)-tert-Butyl (1-(4-bromophenyl)ethyl)carbamate

Product 1

HCID 86631938HCID 86631938, compoundYield 84.4%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 80711,2-DimethoxyethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of 1,1-dimethylethyl [(1S)-1-(4-bromophenyl)-ethyl]carbamate (14.4 g, 48 mmol), tris(dibenzylideneacetone)dipalladium(0) (4.6 g, 4.8 mmol), N-methylpiperazine (22 mL, 200 mmol), BINAP (1.4 g, 4.8 mmol) and tribasic potassium phosphate in ethylene glycol dimethylether (120 mL) was refluxed for 15 hours. On cooling to room temperature, the mixture was diluted with ethyl acetate (100 mL). The organic mixture was extracted using 1N aqueous hydrochloric acid (3×100 mL). The pH of the combined aqueous portions was adjusted to 10 and was then extracted using ethyl acetate (3×100 mL). The combined organic portion was washed with brine then dried over anhydrous sodium sulfate. Filtration and concentration afforded a brown residue which was purified by silica gel column chromatography. Eluting with 0-20% methanol in ethyl acetate, purified fractions were pooled and concentrated to afford 12.9 g, 40.5 mmol (84%) of 1,1-dimethylethyl {(1S)-1-[4-(4-methylpiperazin-1-yl)phenyl]ethyl}carbamate. 1H NMR (400 MHz, d6-DMSO): 7.16 (d, 2H), 6.84 (d, 2H), 4.54 (m, 1H), 3.07 (m, 4H), 2.42 (m, 4H) 2.21 (s, 3H), 1.38 (s, 9H), 1.25 (d, 3H). MS (EI) for C18H29N3O2: 320 (MH+).

Workup

  1. temperaturewas refluxed for 15 hours
  2. extractionThe organic mixture was extracted
  3. extractionwas then extracted
  4. washThe combined organic portion was washed with brine
  5. dry with materialthen dried over anhydrous sodium sulfate
  6. filtrationFiltration and concentration
  7. customafforded a brown residue which
  8. customwas purified by silica gel column chromatography
  9. washEluting with 0-20% methanol in ethyl acetate
  10. custompurified fractions
  11. concentrationconcentrated

Sources & evidence

ORD record
ord-425561343f56434ab75a8799c2203b5d
Source dataset
uspto-grants-2011_09
Patent number
US08012956B2

Reaction notes

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